title: Caenorhabditis elegans histone deacetylase hda-1 is required for morphogenesis of the vulva and LIN-12/Notch-mediated specification of uterine cell fates.
abstract: Chromatin modification genes play crucial roles in development and disease. In Caenorhabditis elegans, the class I histone deacetylase family member hda-1, a component of the nucleosome remodeling and deacetylation complex, has been shown to control cell proliferation. We recovered hda-1 in an RNA interference screen for genes involved in the morphogenesis of the egg-laying system. We found that hda-1 mutants have abnormal vulva morphology and vulval-uterine connections (i.e., no uterine-seam cell). We characterized the vulval defects by using cell fate-specific markers and found that hda-1 is necessary for the specification of all seven vulval cell types. The analysis of the vulval-uterine connection defect revealed that hda-1 is required for the differentiation of the gonadal anchor cell (AC), which in turn induces ventral uterine granddaughters to adopt π fates, leading to the formation of the uterine-seam cell. Consistent with these results, hda-1 is expressed in the vulva and AC. A search for hda-1 target genes revealed that fos-1 (fos proto-oncogene family) acts downstream of hda-1 in vulval cells, whereas egl-43 (evi1 proto-oncogene family) and nhr-67 (tailless homolog, NHR family) mediate hda-1 function in the AC. Furthermore, we showed that AC expression of hda-1 plays a crucial role in the regulation of the lin-12/Notch ligand lag-2 to specify π cell fates. These results demonstrate the pivotal role of hda-1 in the formation of the vulva and the vulval-uterine connection. Given that hda-1 homologs are conserved across the phyla, our findings are likely to provide a better understanding of HDAC1 function in development and disease.
authors.affiliation: Department of Biology, McMaster University, Hamilton, ON L8S 4K1 Canada.
authors.forename: Ayush Vasant
authors.initials: AV
authors.lastname: Ranawade
authors.forename: Philip
authors.initials: P
authors.lastname: Cumbo
authors.forename: Bhagwati P
authors.initials: BP
authors.lastname: Gupta
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D002454:Cell Differentiation; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009024:Morphogenesis / Q000235:genetics*; D009154:Mutation; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014599:Uterus / Q000166:cytology* / Q000254:growth & development; D014844:Vulva / Q000254:growth & development*
chemical_list: D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins; C084226:Egl-43 protein, C elegans; C520083:FOS-1 protein, C elegans; C082460:Lin-12 protein, C elegans; D008565:Membrane Proteins; C497759:N protein, Drosophila; C520004:Nhr-67 protein, C elegans; D016760:Proto-Oncogene Proteins c-fos; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; D051880:Receptors, Notch; D014157:Transcription Factors; C086488:lag-2 protein, C elegans; C508305:HDA-1 protein, C elegans; D006655:Histone Deacetylases
keywords: C. elegans; hda-1; histone deacetylase; morphogenesis; reproductive system